Chronic myelogenous leukemia

Chronic myelogenous leukemia is a clonal hematopoietic malignancy characterized by a balanced translocation between chromosomes 9 and 22 that results in the generation of an abnormal bcr/abl fusion protein with increased tyrosine kinase activity. This abnormal fusion protein has transforming activity for hematopoietic cells in vitro and causes chronic myelogenous leukemia-like myelopoiesis in mice. Chronic myelogenous leukemia progenitor cells display abnormalities in their interactions with bone marrow stroma, perhaps due to defective adhesion molecule function. Conventional therapies for chronic myelogenous leukemia include hydroxyurea, busulfan, or interferon. Treatment with interferon may prolong overall survival, especially in patients who achieve a cytogenetic response. Related donor marrow transplantation can result in long-term survival in more than 65% of patients treated early in the course of disease. For patients without an available matched sibling donor, unrelated donor marrow transplantation or autologous marrow transplantation are alternative therapeutic options.     

Chronic myelogenous leukemia: extending the prospects for cure

Advances in our understanding of the molecular defects underlying this leukemia have led to novel therapeutic approaches that have not only altered the natural history of the disease but also apparently effected cures in some patients. The next step may be to offer the possibility of a cure to all patients. Allogeneic bone marrow and T cell transplantation shows promise in this regard.     

Chronic myelogenous leukemia and acute promyelocytic leukemia: new bone marrow transplantation options

PURPOSE/OBJECTIVES: To describe new bone marrow transplantation (BMT) options for chronic myelogenous leukemia (CML) and acute promyelocytic leukemia (APL), as well as their applications and prognoses, and to describe the role of the oncology nurse in caring for the BMT recipient and options for future nursing research. DATA SOURCES: Published articles, book chapters, and personal experience. DATA SYNTHESIS: Various pretransplant agents and methods are under investigation to improve the outcome and reduce the costs of allogeneic and autologous BMT and peripheral blood progenitor cell (PBPC) transplants. Preliminary results of current studies indicate that autologous BMTs and PBPC transplants have merit as a treatment option in patients with AML and require further research. For patients with APL, BMT usually is reserved for those who fail to achieve or relapse after achieving remission with chemotherapy. Preliminary data show that patients with CML and APL who receive a PBPC transplant engraft more rapidly with decreased morbidity and mortality. CONCLUSIONS: BMT options for patients with CML and APL continue to evolve as advances in pretransplant methods and symptom management become capable of improving the outcome, decreasing costs, and shifting patient care to the outpatient and homecare settings. IMPLICATIONS FOR NURSING PRACTICE: Understanding the marrow transplant options available to patients with CML and APL is essential for nurses. They must stay informed about ongoing improvements in pretransplant processes and symptom-management procedures that reduce BMT morbidity and mortality. Inpatient and outpatient nurses need to collaborate and participate in nursing research to find better ways of providing the best care possible for patients.     

The cellular and molecular environment in leukemia

Identification of normal viability-, growth-, and differentiation-inducing cytokines, the cells that produce them, and how cytokines interact in normal development, has made it possible to identify the cellular and molecular basis of normal development and changes in the developmental program that result in leukemia. When normal cells have been changed into leukemic cells, the malignant phenotype can again be suppressed in various ways. Results on the molecular control of growth, differentiation, and apoptosis in normal myeloid hematopoietic cells, changes in the normal developmental program in myeloid leukemia, and the suppression of malignancy in myeloid leukemia, have shown that (A) malignancy can be suppressed either with or without genetic changes in the tumor cells, (B) suppression of malignancy by inducing differentiation does not have to restore all the normal controls, and (C) genetic abnormalities which give rise to malignancy can be bypassed and their effects nullified by inducing differentiation and apoptosis which stop cells from multiplying.     

Juvenile chronic myelogenous leukemia

Juvenile chronic myelogenous leukemia (JCML) is an aggressive myeloproliferative disorder of childhood that differs both clinically and pathologically from adult type, Philadelphia chromosome positive chronic myelogenous leukemia, and from the other myeloproliferative disorders that are more common in adulthood. The disease can have widely varying clinical presentations and shares many features with the monosomy 7 syndrome and chronic myelomonocytic leukemia. With no specific marker chromosome, establishing the diagnosis can be difficult, and relies on a constellation of clinical, pathologic, and laboratory findings. This article discusses the differential diagnosis of JCML with an emphasis on the pathologic findings and laboratory data that are particularly important for confirming the diagnosis. The sensitivity, specificity, and clinical utility of cell culture colony assays are reviewed. Finally, current knowledge of the biology of JCML and some of the controversies regarding this disease are discussed.     

Interleukin-10 as a regulatory cytokine induced by cellular stress: molecular aspects

Interleukin-10 is an ubiquitous cytokine which plays a major regulatory role in the course of inflammatory responses by downregulating the synthesis of cytokines. In this paper, we summarize the major biological properties of IL-10 and the current knowledge of the molecular mechanisms by which IL-10 inhibits the expression of genes encoding proinflammatory cytokines. We then review the factors upregulating IL-10 synthesis and we present the concept that IL-10 is a stress cytokine produced not only in response to microbial pathogens but also to cellular injuries of diverse origins.     

Autografting for chronic myelogenous leukemia

Two thirds of patients with chronic myelogenous leukemia do not have suitable donors for allogeneic transplantation. As for other leukemias, autografting may potentially be curative, because normal Ph- hematopoietic stem cells persist in the marrow and blood of patients with chronic myelogenous leukemia. Several studies indicate that use of unpurged autologous blood or marrow grafts may extend survival for patients undergoing transplantation in chronic phase. Ex vivo or in vivo purging of chronic myelogenous leukemia marrow or blood prior to autografting may result in increased cytogenetic remissions after transplantation in those patients in whom the Ph+ clone can be eliminated. However, when the Ph+ clone cannot be eliminated, use of purged rather than unpurged autografts provides no advantage and may be associated with increased graft failure. Although sustained cytogenetic remissions have not been observed, autografting may result in a plateau in the survival curve not observed with conventional chemotherapy. Efforts are currently directed toward developing improved methods of purging as well as posttransplantation treatments directed against leukemic cells persisting after myeloablative therapy.     

Stem cells in chronic myelogenous leukemia

This article discusses briefly the molecular consequences of the BCR-ABL fusion gene. It then reviews the current evidence supporting the notion that chronic myelogenous leukemia in its chronic phase is a clonal, hematopoietic, stem cell disease in which malignant hematopoietic stem and progenitor cells respond to "normal" external proliferation and differentiation stimuli, but in which such responses are altered owing to defects in the stem and progenitor cells as a result of the BCR-ABL oncogene.     

Interferon therapy for chronic myelogenous leukemia

Interferon alpha (IFN alpha) has been used in the treatment of chronic myelogenous leukemia (CML). The initial trial was made in 1983 by Talpaz et al. Their first report suggested that IFN alpha treatment could achieve high hematological remission. The cause of the effect was unclear, but may be mediated through interaction cell surface membrane and inhibitory protein production. IFN alpha was related to some T cell immunity, and could be taken to be Ph1 positive cell inhibition by normal T cell. Although IFN alpha therapy has limited use with get Ph1 negative hematopoiesis, intensive treatment of this kind is needed to minimize Ph1 clone, using various therapy combination with IFN alpha.     

Innovative therapy for chronic myelogenous leukemia

Innovative therapies for chronic myelogenous leukemia (CML) have focused mainly on combining autologous transplantation with another modality of therapy for purging of the graft or treatment of the patient after transplant. Of the three categories of innovative therapies, two are based on studies that demonstrate the bcr/abl gene rearrangement in the pathogenesis of CML, whereas the third is based on the observation that allogeneic disparity is important to maintain remissions in CML. The rationale and data supporting these innovative approaches are reviewed in this article and future strategies are discussed.     

c-myc and c-myb expression in acute myelogenous leukemia

Monoclonal antibodies and flow cytometry were used to detect the expression of c-myc and c-myb in the bone marrow (BM) and peripheral blood (PB) cells of patients with acute myelogenous leukemia (AML). The expression of neither gene was correlated with the percent blast cells in the BM or PB nor was there a correlation between c-myc and c-myb expression. A wide range of expression of each gene was found within each FAB type of AML. Patients who had a high proportion of leukemia cells expressing c-myb were less likely to respond to remission induction therapy than patients in whom a low proportion of cells expressed c-myb. This association appears to reflect an inverse relationship between the proportion of cells expressing c-myb and the sensitivity of leukemia cells to the killing effects of chemotherapy in vivo. Treatment outcome was unrelated to c-myc expression.     

Histamine and interleukin-2 in acute myelogenous leukemia

Interleukin-2 (IL-2) activates natural killer (NK)-cells to destroy leukemic blasts from patients with acute myelogenous leukemia (AML), but even aggressive regimens of IL-2 fail to prevent relapse or prolong remission time in AML. Results obtained in studies of NK-cell-mediated killing of AML blasts show that monocytes inhibit IL-2-induced lysis of AML blasts in vitro. Histamine, a biogenic amine, prevents the monocyte-derived, inhibitory signal; thereby, histamine and IL-2 synergize to induce killing of AML blasts. Here we present updated results of a post-consolidation trial in which histamine (0.5-0.7 mg s.c. bid) has been administered together with IL-2 (1 micro/kg s.c. bid) to 22 AML patients (aged 29-79, mean 59) in repeated courses of three weeks, continued until relapse or until a disease-free remission of 24 months. Low-dose therapy with cytarabine and thioguanine was given between the initial courses of histamine/IL-2. In 13 patients, treatment according to this protocol was started in first complete remission (CR1). The mean remission time in CR1 patients is 19 (median 14) months, and 9/13 remain in CR. Nine patients have entered the protocol in CR2 (n=6), CR3 (n=2), or CR4 (n=1). The mean remission time in CR2-4 is 19 (median 21) months, and 6/9 patients remain in CR. Seven out of seven evaluable patients have achieved a duration of CR which exceeds that of the foregoing remission. Histamine has been well tolerated, and 21/22 CR patients have treated themselves at home throughout the trial. We conclude that the putative benefit of histamine treatment in AML should be the focus of a randomized trial.     

Adams-Oliver syndrome: a case with juvenile chronic myelogenous leukemia and chylothorax

We report on a patient with Adams-Oliver syndrome and report new findings: a chylous pleural effusion and juvenile chronic myelogenous leukemia. Also, our patient had congenital heart disease, confirming that heart lesions are a manifestation in this syndrome. The major manifestations of this disorder are summarized. Included are cases not previously recognized as having Adams-Oliver syndrome identified in a literature survey. Distal limb deficiency is commonest with more frequent and more severe involvement of the lower limbs. Scalp defects are the second commonest manifestation, while an underlying skull defect is not infrequent. Cutis marmorata telangiectatica and dilated scalp veins are significant signs of this condition. This review highlights unresolved questions about Adams-Oliver syndrome.     

Chronic myelogenous leukemia received unrelated bone marrow transplantation following surgical resection of cerebral arteriovenous malformation--first case report

We report a 15-year-old boy with chronic myelogenous leukemia who received unrelated bone marrow transplantation (uBMT) after surgical resection of cerebral arteriovenous malformation (AVM). The incidence of cerebral hemorrhage caused by rupture of cerebral ABM in cases of BMT is uncertain. However, since the risk of rupture of AVM was supposed to increase due to both severe thrombocytopenia after intensive chemotherapy and increased intracranical pressure because of total body irradiation (TBI) as preconditioning therapy for BMT, we have first carried out surgical resection of the cerebral AVM, and subsequently performed uBMT. This resulted in a favorable clinical course without serious complications.     

Immunotherapy in the management of myelogenous leukemia

Now that it has been clearly established that tumor-associated antigens exist in acute leukemia in man, as in animals, the possibility of stimulating the patient's immune system to react against them arises. In animal experiments the most effective method of influencing the progress of leukemia after the implantation of living malignant cells has been a combination of nonspecific stimulation of the reticuloendothelial system, with agents such as BCG or Corynebacterium parvum, either with chemotherapy or with specific immunization with irradiated leukemic cells. However, such treatment is only effective if the number of living malignant cells is small as it takes a powerful immune response to overcome even a small number of malignant cells. It is for these reasons that most of the studies in man have been on patients with acute leukemia in remission. Mathé, in 1969, produced evidence that BCG and irradiated allogenic leukemia cells could lengthen the duration of remission in ALL in children. However, later results of intensive combination chemotherapy, together with prophylactic treatment of the central nervous system by Pinkel and his colleagues, were so encouraging that immunotherapy is not felt to be needed and therefore is not being extensively used in this form of leukemia at the moment. The situation in AML, particularly in adults, is completely different. The maintenance of remission with chemotherapy in this type of leukemia is difficult and relapses occur quite rapidly. Various centers have now shown that both remission lengths and overall survival are significantly prolonged by using BCG with or without irradiated allogenic leukemia cells.     

Retinoblastoma: clinical and molecular diagnostic aspects

Retinoblastoma, a tumor of the immature retina concerns babies and young infants in particular. They make up for 14% of malignomas in the first years of life. There are two types of retinoblastoma: In the first two alleles of the gene Rb1 must be inactivated sequentially in the same retinoblast cell until this may escape control. In this case the retinoblastoma is always unilateral and unifocal. This is explained by the lower frequency of two mutations in one retinoblast. The other type, however, is inherited: One allele Rb1 is inactivated in all cells of the organism by mutation. The probability that a second mutation arrives in different retinoblasts is thus high. In this case bilateral multifocal tumors develop. Characterization of the Rb1 gene has permitted identification or at least determination of a haplotype in persons at risk. This knowledge is decisive for early recognition of babies at risk and for genetic counselling.